This project seeks to elucidate abnormalities in catecholamine biosynthesis, metabolism or biological effect in human subjects with heart disease. In particular, alterations in circulating catecholamines and dopamine beta-hydroxylase will be studied in congestive heart failure. In preliminary work we have found that serum dopamine beta hydroxylase activity is low in patients with heart failure and that a circulating inhibitor of enzyme activity which differs from the usual endogenous inhibitors is often present. We plan to purify dopamine beta hydroxylase from normal human plasma in order to develop a radioimmunoassay. Dopamine beta hydroxylase activity and levels by radioimmunoassay in blood from patients with heart failure will be compared to assess the role of the inhibitor. In other experiments the relationship between circulating catecholamines and dopamine beta-hydroxylase will be examined in cardiac patients with and without heart failure at rest, during exercise, during cold pressor tests and after intravenous tyramine administration. The relationships between serum dopamine beta hydroxylase activity or plasma catecholamine levels and changes in clinical course and extent of hemodynamic abnormalities will be investigated. We will also analyze cardiac tissue removed at the time of cardiac surgery for dopamine, norepinephrine, dopamine beta hydroxylase and tyrosine hydroxylase in patients with and without congestive heart failure.